Cesium carbonate → tert-butyl 4-(5-isopropoxy-2-methyl-4-nitrophenyl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 388546Notes

Reaction equation

HRID 388546 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([O:11][CH:12]([CH3:14])[CH3:13])=[CH:4][C:3]=1B1OC(C)(C)C(C)(C)O1.[C:24]([O:28][C:29]([N:31]1[CH2:36][CH:35]=[C:34](OS(C(F)(F)F)(=O)=O)[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:24]([O:28][C:29]([N:31]1[CH2:32][CH:33]=[C:34]([C:3]2[CH:4]=[C:5]([O:11][CH:12]([CH3:13])[CH3:14])[C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=2[CH3:1])[CH2:35][CH2:36]1)=[O:30])([CH3:27])([CH3:25])[CH3:26]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 597645312-(5-Isopropoxy-2-methyl-4-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 59764520tert-butyl 4-(5-isopropoxy-2-methyl-4-nitrophenyl)-5,6-dihydropyridine-1(2H)-carboxylate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-methyl-4-nitro-5-isopropoxy-phenylboronic acid pinacol ester (2.04 g, 6.4 mmol) and 4-Trifluoromethanesulfonyloxy-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (3.2 g, 9.6 mmol) in 110 mL of DME/H2O (10:1 V/V) is added Pd(PPh3)4 (365 mg, 0.32 mmol) and Cs2CO3 (4.2 g, 12.8 mmol). The reaction mixture is heated under N2 at 80° C. overnight. After cooling to room temperature, the reaction is filtered through Celite and the filtrate is diluted with 100 mL of EtOAc, sequentially washed with H2O, brine, and finally concentrated in vacuo. The crude product is purified by silica gel flash chromatography (5%-15% EtOAc in Hexanes as eluent) to afford 4-(5-Isopropoxy-2-methyl-4-nitro-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester as a yellow oil. 1H NMR (CD3OD, 400 Mz): 7.59 (s, 1H), 6.96 (s, 1H), 5.67 (broad s, 1H), 4.73 (m, 1H), 4.06 (m, 2H), 3.65 (m, 2H), 2.37 (m, 2H), 2.25 (s, 3H), 1.50 (s, 9H), 1.33 (d, J=6.0 Hz, 6H).

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe reaction is filtered through Celite
  3. additionthe filtrate is diluted with 100 mL of EtOAc
  4. washsequentially washed with H2O, brine
  5. concentrationfinally concentrated in vacuo
  6. customThe crude product is purified by silica gel flash chromatography (5%-15% EtOAc in Hexanes as eluent)

Sources & evidence

ORD record
ord-3f682c090ee9418aad48af15ec5203f7
Source dataset
uspto-grants-2013_02
Patent number
US08377921B2

Reaction notes

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